Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing100875, China.
Anal Chem. 2022 Dec 6;94(48):16803-16812. doi: 10.1021/acs.analchem.2c03726. Epub 2022 Nov 7.
DNA nanoframeworks, with great biological information and controlled framework structures, exhibit great potentials in biological applications. Their applications are normally limited by unstable structures susceptible to hydrolysis, depurination, depyrimidination, oxidation, alkylation, or nuclease degradations. Herein, to ensure the mechanical and chemical stabilities of DNA nanoframeworks for intracellular applications, biomineralization of multifunctional DNA nanoframeworks with a tetrahedral skeleton is employed. Via silicification, the S-S bond is simultaneously introduced to obtain the silica-armored DNA nanoframeworks (Si-DNA nanoframeworks), mechanically and chemically stabilized for efficient intracellular deliveries. This successfully prevents degradations and leakages of reagents loaded on Si-DNA nanoframeworks, including biomolecular siRNA and small DOX drugs. Furthermore, the nucleic acid strands of the nanoframeworks are labeled with FAM and the quencher, facilitating miRNA detection upon "turn-on" signals from hybridizations. Therefore, the nanoframeworks collapse via double responses of the silica coating (silica acidic dissolution and S-S reduction by GSH) in cancer cells, realizing on-demand reagent release for miRNA detection and synergistic treatments (by siRNA and DOX). Demonstrated by both in vivo and in vitro experiments, the biomineralization has stabilized DNA nanomaterials for biological applications.
DNA 纳米框架具有丰富的生物信息和可控的框架结构，在生物应用中具有巨大的潜力。然而，它们的应用通常受到不稳定结构的限制，这些结构容易受到水解、脱嘌呤、脱嘧啶、氧化、烷基化或核酸酶降解的影响。为了确保 DNA 纳米框架在细胞内应用中的力学和化学稳定性，本文采用多功能 DNA 纳米框架的生物矿化方法。通过硅化作用，同时引入 S-S 键，获得了机械和化学稳定的二氧化硅装甲 DNA 纳米框架（Si-DNA 纳米框架），可有效进行细胞内传递。这成功地防止了装载在 Si-DNA 纳米框架上的试剂（包括生物分子 siRNA 和小 DOX 药物）的降解和泄漏。此外，纳米框架的核酸链被标记为 FAM 和淬灭剂，便于在杂交产生的“开启”信号后检测 miRNA。因此，纳米框架通过二氧化硅涂层的双重响应（二氧化硅的酸性溶解和 GSH 还原 S-S）在癌细胞中坍塌，实现了 miRNA 检测和协同治疗（通过 siRNA 和 DOX）所需的试剂释放。体内和体外实验都证明了生物矿化稳定了用于生物应用的 DNA 纳米材料。
